Helms graduated from the U.S. Air Force Academy in 1980. She received her commission and was assigned to Eglin Air Force Base, Florida, as an F-16 weapons separation engineer with the Air Force Armament Laboratory. In 1982, she became the lead engineer for F-15 weapons separation. In 1984, she was selected to attend graduate school. She received her degree from Stanford University in 1985 and was assigned as an assistant professor of aeronautics at the U.S. Air Force Academy. In 1987, she attended the Air Force Test Pilot School at Edwards Air Force Base, California. After completing one year of training as a flight test engineer, Helms was assigned as a USAF Exchange Officer to the Aerospace Engineering Test Establishment, at Canadian Forces Base Cold Lake in Alberta, Canada, where she worked as a flight test engineer and project officer on the CF-18 aircraft. She was managing the development of a CF-18 flight control system simulation for the Canadian Forces when selected for the astronaut program.

Helms was promoted to major general in August 2009.[1] She served as the Director of Plans and Policy, U.S. Strategic Command, Offutt Air Force Base, Nebraska. She was directly responsible to the U.S. Strategic Command commander for the development and implementation of national security policy and guidance; military strategy and guidance; space and weapons employment concepts and policy; and joint doctrine as they apply to the command and the execution of its missions. She was also responsible for the development of the nation's strategic war plan, strategic support plans for theater combatant commanders and contingency planning for the global strike mission.

In January 2011, Helms was promoted to lieutenant general and assumed duties as commander, 14th Air Force (Air Forces Strategic), Air Force Space Command and Commander, Joint Functional Component Command for Space, US Strategic Command[1][4][5][6]

As a flight test engineer, Helms has flown in 30 different types of U.S. and Canadian military aircraft.[citation needed]

In 2013, Helms was nominated by President Barack Obama to become vice commander of the Air Force Space Command. Senator Claire McCaskill placed a permanent hold on the nomination because Helms had dismissed a charge of a sexual assault and punished Captain Herrera on a lesser charge leading to his dismissal from the USAF, in her role as the General Court-Martial Convening Authority, who is required to review all findings.[7][8] As Helms's lawyer explained, Helms felt the prosecution had failed to prove its case beyond a reasonable doubt.[9][10] Obama eventually withdrew Helms's nomination.[11]

STS-54Endeavour, January 13–19, 1993. The primary objective of this mission was the deployment of a $200-million NASA Tracking and Data Relay Satellite (TDRS-F). A diffuse X-ray spectrometer (DXS) carried in the payload bay, collected over 80,000 seconds of quality X-ray data that will enable investigators to answer questions about the origin of the Milky Way galaxy. The crew demonstrated the physics principles of everyday toys to an interactive audience of elementary school students across the United States. A highly successful extra-vehicular activity (EVA) resulted in many lessons learned that will benefit International Space Station assembly. Mission duration was 5 days, 23 hours, 38 minutes, 17 seconds.

Helms views the topography of a point on Earth from the nadir window of the ISS.

STS-64Discovery, September 9–20, 1994. On this flight, Helms served as the flight engineer for orbiter operations and the primary RMS operator aboard Space Shuttle. The major objective of this flight was to validate the design and operating characteristics of Lidar in Space Technology Experiment (LITE) by gathering data about the Earth's troposphere and stratosphere. Additional objectives included the deploy and retrieval of SPARTAN-201, a free-flying satellite that investigated the physics of the solar corona, and the testing of a new EVA maneuvering device. The Shuttle Plume Impingement Flight Experiment (SPIFEX) was used to collect extensive data on the effects of jet thruster impingement, in preparation for proximity tasks such as space station docking. Mission duration was 10 days, 22 hours, 51 minutes.

STS-78Columbia, June 20 to July 7, 1996, Helms was the payload commander and flight engineer aboard Columbia, on the longest Space Shuttle mission to date (later that year the STS-80 mission broke its record by nineteen hours). The mission included studies sponsored by ten nations and five space agencies, and was the first mission to combine both a full microgravity studies agenda and a comprehensive life science investigation. The Life and Microgravity Spacelab mission served as a model for future studies on board the International Space Station. Mission duration was 16 days, 21 hours, 48 minutes.

STS-101Atlantis, May 19–29, 2000, was a mission dedicated to the delivery and repair of critical hardware for the International Space Station. Helms prime responsibilities during this mission were to perform critical repairs to extend the life of the Functional Cargo Block (FGB). In addition, she had prime responsibility of the onboard computer network and served as the mission specialist for rendezvous with the ISS. Mission duration was 9 days, 20 hours and 9 minutes.

Expedition 2 March 8 to August 22, 2001 was a mission to the International Space Station and Helms was as a member of the second crew to inhabit the International Space Station Alpha. The Expedition 2 crew (two American astronauts and one Russian cosmonaut) launched on March 8, 2001 on board STS-102Discovery and successfully docked with the station on March 9, 2001. The Expedition 2 crew installed and conducted tests on the Canadian-made Space Station Robotic arm (SSRMS), conducted internal and external maintenance tasks (Russian and American), in addition to medical and science experiments. During her stay on board, Helms installed the airlock (brought up on the STS-104 mission) using the SSRM. She and her crewmates also performed a 'fly around' of the Russian Soyuz spacecraft and welcomed the visiting Soyuz crew that included the first space tourist, Dennis Tito. On March 11 she performed a world-record 8 hour and 56 minute space walk to install hardware to the external body of the laboratory module. Helms spent a total of 163 days aboard the space station. She returned to earth with the STS-105 crew aboard Discovery on August 22, 2001.